Evidence-Based Clinical Recommendations Regarding Screening for Oral Squamous Cell Carcinomas

Michael P. Rethman, DDS, MS, William Carpenter, DDS, MS, Ezra E.W. Cohen, MD, Joel Epstein, DMD, MSD, FRCD(C), FDS RCS(Ed), Caswell A. Evans, DDS, MPH, Catherine M. Flaitz, DDS, MS, Frank J. Graham, DMD, Philippe P. Hujoel, MSD, PhD, John R. Kalmar, DMD, PhD, Wayne M. Koch, MD, Paul M. Lambert, DDS, Mark W. Lingen, DDS, PhD, Bert W. Oettmeier Jr., DDS, Lauren L. Patton, DDS, David Perkins, DMD, Britt C. Reid, DDS, PhD, James J. Sciubba, DMD, PhD, Scott L. Tomar, DMD, DrPH, Alfred D. Wyatt Jr., DMD, Krishna Aravamudhan, BDS, MS, Julie Frantsve-Hawley, RDH, PhD, Jennifer L. Cleveland, DDS, MPH, Daniel M. Meyer, DDS; AND for the American Dental Association Council on Scientific Affairs Expert Panel on Screening for Oral Squamous Cell Carcinomas

Background. This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association’s Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions.

Types of Studies Reviewed. The panel members conducted systematic research on MEDLINE, identifying 332 systematic reviews and 1,499recent clinical studies. They selected five systematic reviews and four clinical studies to use as a basis for developing recommendations.

Results. The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in the detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care.

Clinical Implications. The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Key Words: American Dental Association (ADA); biopsy; brush; cancer; carcinoma; squamous cells; evidence-based dentistry; mouth neoplasms; oral cancer; practice guidelines

Abbreviations: ACS: American Cancer Society • ADA: American Dental Association • CDC: Centers for Disease Control and Prevention • HPV: Human papillomavirus • IR: Incidence rate • LED: Light-emitting diode • RCT: Randomized controlled trial

The American Cancer Society (ACS) estimated that there would be 35,720 new cases of cancer in the oral and pharyngeal regions of the United States in 2009, with 7,600 deaths from the disease. When focusing specifically on oral cavities, ACS estimated that in 2009, there would be 23,110 new cases of cancer of the oral cavity (hereafter referred to as “oral cancer”) and 5,370deaths. Nearly 90 percent of these malignancies are squamous cell carcinomas. More than 97 percent of U.S. cases of these cancers occur among adults 35 years and older. Although the incidence rate (IR) of oral and pharyngeal cancers is decreasing overall, the IR of cancers of the tongue, oropharynx, and tonsils are increasing. The 2002–2006 age-adjusted (to the 2000U.S. population) IR of oral and pharyngeal cancers in the United States was 10.3 per 100,000 per year. The age-adjusted IR was more than twice as high among men (15.9) as among women (6.0), as was the mortality rate (men, 4.0; women, 1.5).

Among the groups described in data from the National Cancer Institute’s Surveillance Epidemiology and End Results program, African-American men are at the highest risk of developing oral and pharyngeal cancers of any group in the United States (IR 16.7 per 100,000 per year). The five-year relative survival rate varies widely by stage at the time of diagnosis, from 81.8percent for patients diagnosed in localized stages and 52.1percent for patients with regional lymph node involvement to26.5 percent for patients with distant metastasis. Yet, oral and pharyngeal cancer is diagnosed at a localized stage in only one-third of patients in the United States. The overall five-year relative survival rate for the 1999–2005 period was 61.0percent and varied significantly by race (62.4 percent for white men and 38.2 percent for black men). Much of the racial disparity in survival rates was due to the greater proportion of tumors diagnosed at late stages among black men than among white men.

The report was developed by a panel convened by the American Dental Association (ADA) Council on Scientific Affairs to address the benefits and limitations of oral cancer screening and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. The panel’s work was supported in part by the Centers for Disease Control and Prevention (CDC), Atlanta.

We have excluded squamous cell carcinomas from the lips from this article, because the risk factors, stage-at-diagnosis patterns, morbidity, and mortality of those carcinomas differ from those of cancer in sites in the oral cavity. We also excluded from this report cancers of the oropharynx (including the posterior one-third [base] of the tongue and the tonsils). Although the oral cavity and the oropharynx overlap in the region of the hard and soft palate and tonsils, recent systematic reviews suggest that human papillomavirus (HPV) is a risk factor for cancers of the base of the tongue and the tonsils. In contrast, HPV does not appear to be a significant risk factor for cancer of the anterior two-thirds of the tongue or the remaining oral cavity. The importance of this distinction is highlighted by evidence that HPV-related carcinomas have a better prognosis overall than doing non-HPV–related carcinomas.

The clinical recommendations in this article, which present a critical evaluation and summary of the relevant scientific evidence, do not represent a standard of care. Instead, this report is intended to assist clinicians in the decision-making process. The clinical recommendations should be integrated with the practitioner’s professional judgment and the individual patient’s needs and informed preferences.

This report defines “screening” as the process by which a practitioner evaluates an asymptomatic patient to determine if he or she is “likely” or “unlikely” to have a potentially malignant or “malignant” lesion. In “mass screening” programs, also known as ”community-based” or “population-based” screening, the target group is invited to participate specifically for the purpose of detecting potentially malignant lesions. These screenings may have a specific goal of detecting potentially malignant oral lesions, or they may be broader in scope and involve the assessment of a person’s general oral health status. In a dental setting, the act of “screening” for oral cancer occurs when a patient reports for care This often is referred to as an” opportunistic screening.”

The practitioner obtains a health history to assess the patient’s general health and risk of developing the disease. A thorough health history review should yield information about the patient’s tobacco and alcohol use, hospitalization history, surgery experience, dietary patterns, medication regimen, and other illnesses. Investigators have observed an increased risk of developing oral cancer with increasing age, in people who use tobacco, in people who consume alcohol heavily (for men an average of more than two drinks daily and for women an average of more than one drink daily), in people who have a history of upper aerodigestive tract cancer and in people who have certain inherited diseases, such as Fanconi anemia. The practitioner also conducts a visual and tactile examination (referred to as “examination” throughout this report to detect the presence of any oral abnormality. Some of the mucosal abnormalities noted in the examination could be potentially malignant or malignant lesions. This examination should not be viewed as a series of distinct sub-segments intended to detect individual diseases. Screening for oral cancer is but one component of the comprehensive patient evaluation provided by dentists to detect all forms of oral pathoses, including those of neoplastic, infectious, reactive/inflammatory, or developmental origin.

Clinical signs of cancer. Invasive cancer. Clinical signs of invasive cancer can include induration; persistent ulceration; tissue proliferation or destruction; red and white color variegation; lack of mucosal mobility; progressive growth or enlargement of the affected site; pain or dysesthesia; paresthesia or loss of function; and cervical lymphadenopathy. Most oral squamous cell carcinomas exhibit one or more of these clinically, with signs that are often identifiable during a routine examination.

Early-stage cancer. Clinical features of oral lesions identified during their routine visual and tactile examination that might raise suspicion of potential malignancy include sharp or distinct margins, a component (color variation), a non-homogenous white component (surface irregularity), persistent ulceration, and size larger than 1 centimeter. The clinician also should view with suspicion any persistent or progressive lesion of the ventrolateral tongue or the floor of the mouth (both of which are high-risk sites for oral squamous cell carcinoma).

Early-stage lesions are often asymptomatic and may mimic other conditions, whereas others may not be readily evident in a routine examination. Also, because malignant and benign lesions may not be clinically distinguishable, the clinician cannot predict the biological relevance of lesions on the basis of their physical features alone.

Adjunctive screening aids are marketed to assist clinicians with the detection of early cancerous changes or for the assessment of the biological relevance of mucosal lesions.

Devices intended to assist in lesion detection. These devices feature special light sources designed according to principles of tissue reflectance and tissue autofluorescence to enhance the oral examination process. Manufacturers of these devices claim that they may help the practitioner visualize oral mucosal abnormalities that are not readily detectable with conventional operatory lighting, or that they can enhance the practitioner’s ability to specifically identify potentially malignant lesions.

Devices based on tissue reflectance. The devices are claimed to help practitioners detect oral mucosal abnormalities that would otherwise be difficult to discern routine visual examination. The following commercial tissue-reflectance–based devices are available in the United States: Microlux/DL (AdDent, Danbury, Conn.), Orascoptic DK (Orascoptic, a Kerr Company, Middleton, Wis.), and ViziLite Plus (Zila Pharmaceuticals, a  division of Tolmar, Phoenix).

ViziLite Plus uses a disposable chemiluminescent light packet, and the MicroLux/DL and Orascoptic DK units use a reusable, battery-powered light-emitting diode (LED) light source that provides a similar blue-white (440-nanometer range) illumination. Each system employs a 1 percent acetic acid wash before the use of its respective light source. Under blue and white illumination, the abnormal squamous epithelium is reported to be distinctly white (act white). ViziLite Plus also provides a toluidine blue solution (Blue, Zila Pharmaceuticals), which is intended to mark an act of white lesion for subsequent biopsy.

MicroLux/DL and Orascoptic devices use a similar reusable insert or probe to transmit light from the LED source in the handpiece to the oral tissues. Both units are marketed as multiuse devices because their handpieces are designed to accept a separate transillumination tip for the detection of tooth fractures or caries, as well as another insert that provides the dentist with a lighted mirror.

Device-based autofluorescence. VELscope (LED Dental, Burnaby, British Columbia, Canada) is marketed as an adjunct to visual examination in the identification of oral mucosal abnormalities that otherwise may not be apparent with conventional operatory lighting. Under the blue-light excitation(400–460 nm) provided by the unit, normal oral mucosa emits a pale green autofluorescence when viewed through the filter set incorporated within the handpiece. In contrast, the manufacturer states that abnormal tissue exhibits decreased levels of autofluorescence and appears dark compared with the surrounding tissue. The manufacturer cautions, however, that loss of autofluorescence is not strictly limited to epithelial abnormalities and can be seen with prominent surface vascularity, including areas of inflammation and melanin pigmentation.

Device-based autofluorescence and tissue reflectance. Identify 3000 (Trimira, Houston) combines the technologies of tissue reflectance and autofluorescence with a conventional white light source. It is claimed to help the practitioner identify oral mucosal abnormalities that otherwise may not be apparent. It is also claimed to help the practitioner discern the superficial vascularity of the tissue.

The device is intended to assist in lesion assessment.

This type of device is designed to help practitioners assess the biological relevance of mucosal lesions and determine the need for surgical biopsy and tissue diagnosis. By providing a transepithelial (full-thickness) collection of disaggregated cells from the lesional tissue, the device allows subsequent identification of atypical cells that may indicate malignancy.

Device-based transepithelial cytology. The OralCDx BrushTest (OralCDx Laboratories, Suffern, N.Y.) is intended for the evaluation of lesions that do not immediately raise suspicion of cancer. The Oral CDx BrushTest consists of a disposable, circular plastic brush that the clinician rubs or rotates against the lesion until he or she observes pinpoint bleeding. The clinician uses this clinical endpoint to confirm penetration of the basement membrane and acquisition of a transepithelial (full-thickness) sample. After the clinician transfers the sample to a glass slide, he or she applies a fixative solution, then returns the fixed sample to the company for computer-assisted analysis and interpretation by a pathologist.

The specimen analysis will yield one of four results:

– incomplete specimen—too few cells from all cell layers; 

– negative—no evidence of abnormal cells; 

– atypical—abnormal epithelial cells of uncertain significance; 

– positive—definitive evidence of dysplastic or cancer cells. 

In the case of atypical or positive results, the company recommends surgical biopsy of the lesion. This is because the test results are limited to reporting the presence or absence of cellular abnormalities and do not provide a final diagnosis.

The ADA Council on Scientific Affairs convened a panel to evaluate the available evidence regarding oral cancer screening and the use of adjuncts. The Council selects panelists on the basis of their expertise in the relevant subject matter. At a workshop held at ADA Headquarters April 13–15, 2009, the panel evaluated the published evidence and developed evidence-based clinical recommendations for oral cancer screening and the use of adjuncts.

Conflict-of-interest disclosures. The panel comprised 20 people who represented a broad range of expertise. Each panelist completed a standard conflict-of-interest questionnaire.

Literature search. Staff members of the ADA Center for Evidence-Based Dentistry searched MEDLINE through PubMed to identify systematic reviews that addressed the four clinical questions. On the basis of the inclusion and exclusion criteria, they identified five systematic reviews. They conducted a second search to identify clinical studies published after the last search date within the systematic reviews. They identified four additional clinical studies. Appendix 1 in the supplemental data online provides a detailed description of the search methodology and the inclusion and exclusion criteria, as well as a list of excluded publications.

Data synthesis and critical appraisal. The panel performed a qualitative synthesis of data from the included studies in a narrative format. For the included studies, they performed a quality assessment of individual articles using standard U.S. Preventive Services Task Force methodology to determine internal and external validity. The panel asked Dr. Patton and Epstein, authors of a systematic review of adjunctive screening devices, to update the results of their systematic review with data from the three included clinical studies of screening devices.

Grading evidence statements and clinical recommendations. On the basis of the included studies, the panel developed evidence statements and graded them according to a system developed by Shekelle and colleagues. The panel developed clinical recommendations based on its interpretation of this evidence. They classified clinical recommendations according to the strength of the evidence that formed the basis for the recommendation, again by using a system modified from that of Shekelle and colleagues. The classification of the recommendation directly reflects the level of scientific evidence that supports the recommendation.

Process for developing clinical recommendations. When the panel was unable to reach a consensus when translating evidence into clinically relevant recommendations, it used a majority vote to make final determinations.

Review process. The panel submitted its clinical recommendations for comment to both internal and external scientific experts and organizations. After reviewing all submitted remarks, the panel revised its recommendations where appropriate. The ADA Council on Scientific Affairs approved the final clinical recommendations.

Role of the funding source. The work of this panel was commissioned by the Council on Scientific Affairs and was funded jointly by the ADA and CDC.

The panel came to the following conclusions on the basis of the evidence. The corresponding grade of evidence appears in parentheses.

– While the stage of cancer at diagnosis has an impact on treatment decisions and resultant health outcomes, community-based screening by means of visual and tactile examination in the general adult population intended to detect early and advanced oral cancers may not alter disease-specific mortality(Ib). 

– Community-based screening by means of visual and tactile examination may decrease oral cancer-specific mortality among people who use tobacco, alcohol, or both(Ib). 

–Screening by means of visual and tactile examination may result in the detection of oral cancers at early stages of development (stages I and II) (Ib). 

– In asymptomatic patients seeking dental care, there is insufficient evidence to determine whether screening by means of visual and tactile examination to detect potentially malignant and malignant lesions alters disease-specific mortality(III). 

– There is insufficient evidence that commercial devices based on autofluorescence enhance visual detection of potentially malignant lesions beyond that achieved through a conventional visual and tactile examination (III). 

– There is insufficient evidence that commercial devices based on tissue reflectance enhance visual detection of potentially malignant lesions beyond that achieved through a conventional visual and tactile examination (III). 

–There is insufficient evidence to assess the validity of transepithelial cytology of seemingly innocuous mucosal lesions (III). 

–In suspicious mucosal lesions with high potential for malignancy, transepithelial cytology has validity in identifyingdisaggregateddysplastic cells (III). 

A conclusion of “insufficient evidence” does not necessarily mean that the intervention is or is not effective, but instead means that the panel did not find sufficient evidence to support a recommendation.

The rationale for recommendations: oral cancer screening. Screening by means of examination can detect potentially malignant and malignant lesions at an early stage. Yet just as clinical features alone cannot reliably distinguish between benign and malignant lesions, neither can the clinician accurately predict the likelihood or rate of progression to cancer (malignant transformation) for a given potentially malignant lesion on the basis of routine biopsy, histopathological examination, and diagnosis. Further complicating matters is the relatively low prevalence of potentially malignant and malignant oral mucosal lesions in the general U.S. population. In relatively rare diseases, only a small proportion of lesions that yield positive screening results will be true positives, even when the clinician uses a screening test with high sensitivity and specificity.

Researchers who conducted a randomized controlled trial (RCT) in India suggested that screening by means of visual and tactile examination to detect potentially malignant lesions may not lower the disease-specific mortality rate in the general adult population, even in a country such as India, which has a higher prevalence rate of oral cancer than does the United States. The evidence also suggested that a community-based screening program (that is, examination of a target group of people whose participation is solicited via invitation) that identified people with early and advanced stages of the disease in the general adult population may not lower mortality rates. However, members of the panel questioned the applicability of this evidence to asymptomatic patients seeking dental care in the United States.

Successful translation of oral cancer screening regimes introduced mortality requires that patients receive a confirmatory diagnosis, have continual access to a health care delivery system, and complete a curative treatment regimen. In the India-based RCT, only 63 percent of the patients whose screenings (by trained health care workers) yielded positive results for leukoplakias, erythroplakia, submucous fibrosis, or oral cancer complied with referrals to a physician for confirmation and, if warranted, surgical biopsy. Furthermore, in that study, a greater percentage of the cases were diagnosed in stages III and IV of the diseases compared with those diagnosed in stages I and II Of the122 patients whose cancer was diagnosed in early stages (stages I and II), only five were “low-risk” patients (nonusers of tobacco and alcohol).  Although these articles did not provide treatment details, the panel contacted the authors to obtain additional. T information the authors reported that one-third of patients who complied with referrals did not receive care with the intent to treat (Dr. R. Sankaranarayanan and Dr. R. Muwonge, electronic and S. communication kept. 10, 2009). The lower IR of oral cancer in the United States makes it difficult to perform a similar RCT in this country, which may explain in part the paucity of U.S. data supporting a positive health outcome resulting from oral cancer screening.

The extent (stage) of cancer at diagnosis guides treatment. But members of the panel found insufficient evidence to determine whether screening favorably altered disease-specific outcomes—including treatment-related morbidity (such as esthetics, speech, and swallowing)—or affected patients’ quality of life, either positively or negatively. Furthermore, in the routine setting of asymptomatic patients seeking dental care, there is insufficient evidence to determine whether screening by means of visual and tactile examination to detect potentially malignant and malignant lesions alters disease-specific mortality.

A disease-screening regimen should include a comparison of the risks of intervention and nonintervention and the benefits of intervention and nonintervention. For example, a screening program may fail to detect a disease that otherwise might be successfully treated. Screening also may reveal highly aggressive life-threatening cancers whose outcome may not have been changed by early detection—that is, for which treatment would be futile. In addition, screenings may falsely identify nondiseased sites as diseased and may detect diseases that, if undetected, might not ever interfere with a patient’s life. The latter two scenarios can result in needless worry, unnecessary interventions, and wasted resources.

In the context of the limited evidence available, the panel members agreed that for oral squamous cell carcinomas, the evidence suggests that routine oral screenings (consisting of visual and tactile examinations) of asymptomatic patients can detect some potentially dangerous lesions at earlier stages. This suggests the potential for less invasive treatments with less attendant morbidity and improved mortality—if one makes the plausible assumption that a number of these early lesions would have progressed had there been no intervention. As noted previously, however, there is insufficient evidence in this context to determine whether early detection and treatment alter disease-specific outcomes, such as morbidity or mortality, or whether screening affects patients’ quality of life, either positively or negatively. Yet, despite the likelihood of biases inherent in this comparison, the five-year survival rate of patients with early-stage oral squamous cell carcinomas (stages I and II) is higher than that of patients with cancers detected at later, more advanced stages.

In light of the lack of evidence regarding the effects of routine screening of asymptomatic dental patients on morbidity or mortality in the United States, the panel weighed the potential benefits and the potential risks of such screening in making its recommendations. The panel agreed that routine screening might extend the lives of some patients but also might have associated risks for many others. Applying their clinical experiences and professional judgment to the available evidence, the majority of the panel members concurred that the potential life-saving benefits for the smaller percentage of patients with treatable malignant lesions were more important than the potential physical and psychological harms incurred by the higher percentage of patients with benign or nonprogressive lesions. Because of these considerations, the majority of the panel members stressed the need for clinicians to remain alert for signs of potential malignancy when performing routine visual and tactile examinations in dental patients, especially those with a history of tobacco and heavy alcohol use.

Recognizing the need to minimize false-positive screening results, the panel suggested that clinicians follow up with patients within seven to 14 days after first removing or treating any potential cause(s) of lesions to confirm persistence or progression of lesions, especially in lesions that initially appeared innocuous. Because many oral soft-tissue lesions are transient and will resolve, if the suspected etiologic factor is removed or treated (for example, eliminating a local irritant or dental trauma), limiting biopsies to only those lesions that persist may improve screening accuracy. When a clinician observes a persistent or progressive lesion, he or she may consider prompt referral to a dental or medical provider with advanced training and experience in the diagnosis of oral mucosal disease before performing tissue. T biopsy will further limit the possible morbidity associated with false-positive results. However, should a clinician suspect potential malignancy in a mucosal abnormality during the initial examination, he or she may want to perform a biopsy immediately or ensure that the patient receives prompt evaluation (and possible biopsy) by a dental or medical care provider who has advanced training and experience in the diagnosis of oral mucosal disease.

When a definitive diagnosis is needed, a clinician should perform a surgical biopsy with subsequent specimen processing and histopathological examination. The panel also suggested that clinicians understand and clearly communicate to the patient the benefits of early diagnosis and the potential risks of assisting the patient in healthcare decision-making.

Visualization devices. In studies published thus far, researchers have evaluated ViziLite, ViziLite Plus, and VELscope. There is no published evidence regarding the utility of MicroLux/DL, Orascoptic DK, or Identafi 3000. Overall, there is insufficient evidence that the commercially available devices based on tissue reflectance (ViziLite and ViziLite Plus) and autofluorescence (VELscope) improve the detection of potentially malignant lesions beyond that of a conventional visual and tactile examination.

Clinicians should be aware that understanding the etiology of cancer along with the differences in the clinical presentation of other similar abnormalities remains of primary importance.

Two studies by ViziLite showed the device to have high sensitivity but low specificity when researchers confirmed its findings through histopathological examination. There is some evidence that VELscope may improve the determination of surgical margins and selection of the optimal biopsy site in large or multifocal lesions or during surgery. The manufacturer has extrapolated this evidence to suggest that the device could help identify potentially malignant lesions that may not be readily apparent or visible to the naked eye. However, to our knowledge, no peer-reviewed publications support this claim. Overall, visualization aids may affect a lesion’s appearance in terms of brightness, texture, and delineation of margins and in patients with previously detected lesions, but they have not been shown to enhance the practitioner’s ability to identify potentially malignant lesions specifically or to identify lesions not visible under normal operatory lighting. Furthermore, there is insufficient evidence that these devices improve patient compliance or aid in patient education.

As mentioned earlier, a visual examination cannot specifically identify the small proportion of lesions that exhibit early cancerous changes. Using currently available visualization aids does not allow a clinician to overcome this limitation. Clinicians should be aware that understanding the etiology of cancer along with the differences in the clinical presentation of other similar abnormalities remains of primary importance. The use of these devices can be associated with an increased risk of false-positive findings. The panel found insufficient evidence to make a recommendation for or against general dentists’ use of these devices in their patients.

Transepithelial cytology of disaggregated cells (Oral CDx BrushTest). While the results of the Oral CDx Brush Test may help the practitioner identify the presence of atypical cells in seemingly innocuous mucosal lesions, clinicians must note that atypical findings are frequently obtained when this test is performed on inflammatory or reactive lesions. Receiving an “atypical” test result is more common when the BrushTest is used on an inappropriate type of lesion, such as a pigmented mucosal lesion. The application of the BrushTest to common mucosal abnormalities that may mimic precancerous changes clinically, such as reactive frictional keratosis, without observation during a follow-up examination seven to 14 days after initial detection also raises the probability of receiving an “atypical” result. These results (essentially false positives) may lead, in turn, to the unwarranted referral of the patient for further evaluation by a dental or medical care provider with advanced training and experience in the diagnosis of oral mucosal disease; they may even trigger tissue biopsies that otherwise might have been deemed unnecessary by practitioners who have advanced training and experience in the diagnosis of oral mucosal disease. Thus, there is insufficient evidence to support a recommendation for or against the use of Oral CDx BrushTestin in seemingly innocuous mucosal lesions.

In clinically suspicious lesions, the Oral CDx BrushTest has validity in identifying disaggregated dysplastic cells. Despite this, the panel members believe that clinically suspicious lesions should be biopsied immediately for diagnosis. However, the panel members believe that the Oral CDQ BrushTest may prove useful for patients in specific clinical situations. These might include patients who have multiple lesions throughout the oral cavity and no history of oral cancer (as an alternative to multiple scalpel biopsies); non-compliant patients who are unlikely to return for follow-up care or comply with an immediate referral for further evaluation by a dental or medical care provider who has advanced training and experience in the diagnosis of oral mucosal disease; adults who have physical and intellectual disabilities or a complex medical status who cannot safely tolerate surgical procedure or who have severe access-to-care restraints; and those who have a history of previously treated upper aerodigestive tract cancer.

Stand-alone use of toluidine blue. Toluidine blue (also known as tolonium chloride) is a vital dye that differentially stains abnormal tissues, including those that are premalignant and malignant in nature. While not approved by the U.S. The Food and Drug Administration for use as a stand-alone adjunct for oral cancer detection in the United States, toluidine blue, is used widely in other parts of the world as a means of assessing mucosal abnormalities for evidence of possible malignant or premalignant changes.

In people with a history of oral cancer or people older than50 years who smoke and drink, toluidine blue may assist dental or medical care providers who have advanced training and experience in the diagnosis of oral mucosal disease in the clinical assessment of potentially malignant lesions. However, there is insufficient evidence to recommend for or against the stand-alone use of toluidine blue to enhance the identification of potentially malignant lesions in the general population.

A number of promising new technologies have been proposed to improve the effectiveness of early oral cancer detection, including the use of saliva as an oral cancer screening platform; the use of cytology plus ploidy analysis; loss-of-heterozygosity analysis; identification of bacterial markers in biofilms; identification of an individual or multiple protein biomarkers revealed via tissue biopsies; the use of in vivo molecular probes and paints; and the use of other imaging modalities. We have not reviewed the technologies in this article.

These recommendations are intended to help practitioners with issues related to the assessment and detection of oral cancer. They should not be viewed as rigid guidelines or standards of care, but as evidence-based recommendations to be used together with each practitioner’s professional judgment and experience in the context of the needs or informed preferences of the individual patient. Although the panel formulated these recommendations on the basis of a careful review of published scientific evidence, the panel acknowledges that the current literature related to oral cancer screening is not robust. Additional well-designed epidemiologic studies and prospective controlled clinical trials are needed. Regarding screening adjuncts, the panel found insufficient evidence to support recommendations for or against the use of light-based technologies compared with conventional operatory lighting alone. While the OralCDx BrushTest has demonstrated validity as an adjunct to lesion assessment in specific clinical situations, practitioners must remember that the diagnostic gold standard for oral cancers and potentially malignant lesions continue to be a histopathological examination of surgical biopsy specimens.

Screening for oral cancer is only one component of a thorough oral examination and evaluation that includes obtaining patient history and an oral cancer risk assessment. As mucosal lesions are noted, a re-evaluation of seven to 14 days to confirm lesion persistence can reduce the potential for errors in clinical diagnosis. Similarly, the clinician can reduce the risk of performing unnecessary biopsies by obtaining an opinion from a dental or medical care provider who has advanced training and experience in the diagnosis of oral cancer and its precursor lesions.

Dr. Rethman is a periodontist in Honolulu; an adjunct assistant professor at the College of Dentistry, Ohio State University, Columbus; and an adjunct assistant professor at Baltimore College of Dental Surgery, University of Maryland. He is also the chair of, the American Dental Association’s Council on Scientific Affairs.

Dr. Carpenter is a professor and the chair of, Department of Pathology and Medicine, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco. He also represented the American Dental Association’s Council on Access, Prevention, and Interprofessional Relations on the expert panel.

Dr. Cohen is an associate professor at, Department of Medicine, University of Chicago Medical Center.

Dr. Epstein is a professor in the Department of Oral Medicine and Diagnostic Sciences, College of Dentistry; a professor, Department of Otolaryngology-Head and Neck Surgery, College of Medicine; and a professor, Cancer Center, at the University of Illinois at Chicago.

Dr. Evans is the associate dean of prevention and public health sciences, College of Dentistry, and the University of Illinois at Chicago.

Dr. Flaitz is a professor at, Department of Diagnostic Sciences, and a professor at, Department of Pediatric Dentistry, University of Texas Dental Branch in Houston.

Dr. Graham maintains a private practice in orthodontics in Teaneck, N.J., and is a senior attending dentist in the Orthodontics Department of Dentistry at Montefiore Medical Center in Bronx, N.Y. He is also the immediate past chair of, the American Dental Association Council on Dental Practice, and represented the Council on the expert panel.

Dr. Hujoel is a professor at, Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle.

Dr. Kalmar is a professor, Division of Oral and Maxillofacial Surgery, Pathology and Anesthesiology, College of Dentistry, The Ohio State University, Columbus. He also represented the Academy of Oral and Maxillofacial Pathology on the expert panel.

Dr. Koch is a professor at, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medicine, Baltimore. He also represented the American Head and Neck Society on the expert panel.

Dr. Lambert is the chief of staff at, Department of Veterans Affairs Medical Center, Boise, Idaho. He also represented the American Association of Oral and Maxillofacial Surgeons on the expert panel.

Dr. Lingen is an associate professor at, Department of Pathology, University of Chicago Medical Center. He also represented the American Dental Association’s Council on Scientific Affairs on the expert panel.

Dr. Oettmeier maintains a private practice in general dentistry in Leawood, Kansas. He also represented the American Dental Association’s Council on Dental Benefits Programs on the expert panel.

Dr. Patton is a professor and the interim chair of, Department of Dental Ecology, School of Dentistry, the University of North Carolina at Chapel Hill.

Dr. Perkins maintains a private practice in general dentistry in Bristol, Conn. He also represented the American Dental Association’s Council on Education and Licensure on the expert panel.

Dr. Reid is the chief, Modifiable Risk Factors Branch, Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Md.

Dr. Sciubba is a retired professor and director of dental and oral medicine, School of Medicine, Johns Hopkins University, Baltimore, and a member of the consulting staff, The Milton. Dance Head & Neck Center, Greater Baltimore Medical Center.

Dr. Tomar is a professor at, Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville. He is also the president of the American Association of Public Health Dentistry.

Dr. Wyatt maintains a private practice in general dentistry in College Park, Ga., and is an assistant professor of oral rehabilitation at, School of Dentistry and Medical College of Georgia, Atlanta. He also represented the National Dental Association, the expert panel.

Dr. Aravamudhan is the assistant director, Center for Evidence-Based Dentistry, Division of Science, American Dental Association,211 E. Chicago Ave., Chicago, Ill. 60611, e-mail “aravamudhank@ada.org“.Address reprint request for Dr. Aravamudhan.

Dr. Frantsve-Hawley is the director, Research Institute and Center for Evidence-Based Dentistry, Division of Science, American Dental Association, Chicago.

Dr. Cleveland is a Dental Officer, Surveillance and Investigations and Research Branch, Division of Oral Health, Centers for Disease Control and Prevention, Chamblee, Ga.

Dr. Meyer is the director of, Division of Science and Senior Vice President, Science and Professional Affairs, American Dental Association, Chicago.

Disclosures. Dr. Carpenter has received compensation from OralCDx Laboratories in Suffern, N.Y., for lectures he has presented. Dr. Epstein is conducting an ongoing study with Zila Pharmaceuticals (Phoenix) and served on the company’s medical advisory board until 2007 and has given presentations supported by the company. Dr. Flaitz is a research investigator in a clinical trial funded by Trimira, Houston, investigating the use of the Identafi 3000for the detection of oral lesions, and is a funded presenter for educating the public about this new device; she was a funded lecturer for Oral CDx Laboratories; she received “in-kind” products to assist in teaching and for continuing education programs from Oral CDx BrushTest (CDx Laboratories), ViziLite (Zila Pharmaceuticals), Identafi 3000 (Trimira), MicroLux/DL (AdDent, Danbury, Conn.)and VELscope (LED Dental, Burnaby, British Columbia, Canada). Dr. Sciubba has received compensation from Oral CDx Laboratories for the lectures he has presented. Dr. Wyatt was lectured for and was compensated financially by LED Dental.

The work of the American Dental Association’s Council on Scientific Affairs Expert Panel on Screening for Oral Squamous Cell Carcinomas was supported in part by the Centers for Disease Control and Prevention in Atlanta.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The American Dental Association Council on Scientific Affairs and its expert panel thanked Jane McGinley, RDH, MBA, manager, fluoridation and preventive health activities, and the American Dental Association, Chicago, for her contribution to the project.

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